Abstract
This study aims to explore the anti-tumor activity of Sulforaphane (SFN) alone and combined with Akt/mTOR pathway inhibitors as well as the potential molecular mechanism in esophageal squamous cell carcinoma (ESCC). MTT assay, clone formation experiment, wound healing assays, flow cytometry, Western blot and xenograft experiment were used to test the effects and molecular mechanism of SFN alone or combined with Akt/mTOR inhibitors on proliferation, migration, cell cycle phase, apoptosis of ESCC cells and tumor growth, respectively. The results showed that SFN significantly inhibited the viability and induced apoptosis of ECa109 and EC9706 cells in a dose-dependent manner by increasing the expression of the apoptotic proteins Cleaved-caspase 9. SFN combined with PP242, but not MK2206 and RAD001, had synergetic inhibition effects on the proliferation of ESCC cells. Moreover, the combination of SFN and PP242 had better inhibiting efficiency on clone formation, migratory, cell cycle phase and the growth of xenografts of ESCC cells, as well as the more powerful apoptosis-inducing effects on ESCC cells. Results of protein expression showed that PP242 abrogated the promotion effects of SFN on p-p70S6K (Thr389) and p-Akt (Ser473). These foundings demonstrated PP242 enhances the anti-tumor activity of SFN by blocking the activation of Akt/mTOR pathway by SFN in ESCC.
mTOR Inhibitor PP242 Increases Antitumor Activity of Sulforaphane by Blocking Akt/mTOR Pathway in Esophageal Squamous Cell Carcinoma
